Human Antibodies to Tick-borne Flaviviruses (Czech Science Foundation and Swiss National Science Foundation, international co-operation project Czech Republic- Switzerland, 2021-2023, P.I. Daniel Růžek)
National Centre of Competence MATCA: Materials, Advanced Technologies, Coatings and their Applications (Technology agency of the Czech Republic, 2021-22, coordinator: Václav Hönig)
Laboratory of Arbovirology is one of the members of the consortium NCC MATCA: Materials, Advanced Technologies, Coatings and their Applications. Currently, we are working with other two members of the consortium from the Institute of Physics of the Czech Academy of Sciences and Faculty of Science, University of South Bohemia on a subproject focused on detection of SARS-CoV-2 coronavirus, causative agent of COVID-19, by the means of a biochip.
Methodological platform for prompt reaction to viral pandemics: methods of universal diagnostic and treatment of COVID-19 (Technology Agency of the Czech Republic - program Gamma, 2020-2022, P.I.: Václav Hönig)
Current COVID-19 pandemics has revealed several weak sections in the diagnostics and surveillance systems when it comes to a massive spread of an infection. Low accessibility of quick and reliable diagnostic tools results in delay in determination of diagnosis as well as implementation of effective anti-epidemic measures. The main cause of the delay is associated with spatial and temporal separation of the place of primary sampling and sample testing. The main aim of this project is to develop a rapid and reliable "point of care" testing tool, allowing testing directly at the place of sampling/primary care of the patient. The testing kit is based on the technology of isothermal amplification, which allows linking the simplicity of carrying out an antigen test with the specificity and reliability of a standardized laboratory RT-qPCR.
The part of the project is focused on the development and optimization of a method for the selection of potential convalescent plasma donors for therapeutical purposes. As the causal anti-SARS-CoV-2 therapy is still not available, administration of convalescent plasma represents one of the scarce therapeutical interventions in COVI-19 critically ill patients. As the antibody response is highly variable in the sense total of antibody titer as well as neutralization capacity, it is critical to carefully select the donors of convalescent plasma. We have adapted and optimized a virus neutralization test to be able to identify producers of potent neutralizing antibodies. The biggest advantage of this test is, that it tests the real capacity of the sera to neutralize the virus and not only antibody binding like conventional ELISA-based methods. The test is now routinely provided as a service for multiple hospital transfusion departments.
Neurovascular unit cells interactions leading to the blood-brain barrier breakdown during tickborne encephalitis (Czech Science Foundation, 2020-2023, P.I.: Martin Palus)
Tick-borne encephalitis is a major public health threat among zoonotic arbovirosis. Despite the medical importance of this disease, there is no specific treatment and crucial steps in pathogenesis are poorly characterized. The infection results in neurodegeneration by a mechanism that is not yet fully understood, but it is known that the structural and functional
integrity of the blood-brain barrier (BBB) is compromised and that these alterations have impacts on the development of TBE. We are going to challenge the hypothesis leading to the identification of key features of a potential mechanism of disruption of endothelial barrier integrity during the course of TBE virus infection through the activation of neighboring cells. No detailed study of disease in the CNS can be complete without consideration of all participating cell types (astrocytes, pericytes, microglia, and endothelial cells) and their interactions within the microenvironment of human BBB. It is hoped that this proposal will instill a new appreciation for the human neurovascular cell interactions during TBE development.
We are going to study TBEV interactions with human neurovascular unit cells, reveal the mechanisms of their injury, describe the interaction of the infected cells with other key cell types in the CNS, and identify the molecular aspects leading to blood-brain barrier failure.
Molecular mechanisms of tick-borne encephalitis pathogenesis (Czech Science Foundation, 2020-2023, P.I.: Daniel Růžek)
Tick-borne encephalitis (TBE) represents one of the most serious neuro-infections in Europe and Northeastern Asia. Despite the medical importance of this disease, the biology of the virus as well as the mechanisms of pathogenesis of TBE remain poorly understood. Within this project, we study several aspects of TBE virus biology to identify mechanisms of viral neuroinvasion. Moreover, we address the key questions related to the role of immunopathology in the development of TBE. Our preliminary data strongly indicate that the immune response is an important cause of neuron death. This is in contrast to the prevailing hypothesis that neuronal loss is mediated solely by virus infection.
This project aims at identifying viral virulence determinants, the mechanism(s) by which the virus invades the host brain, and how the infection triggers exuberant immune responses.
Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents a serious viral neuroinfection of humans. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In humans, TBEV may produce a variety of clinical symptoms, from an asymptomatic disease to a fever and acute or chronic progressive encephalitis. This is influenced by a variety of factors, e.g. inoculation dose and virulence of the virus, age and immune status of the host, but also, as our preliminary results strongly suggest, by susceptibility based on host genetic background. Within this research project, we have studied differences in the clinical course of tick-borne encephalitis and its genetic determination. As a model for TBE, recombinant congenic mouse strains were used, since these mice develop TBE of various severity, and this correlates with the situation in humans.